CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Radiation and Chimeric Antigen Receptor T-cell Therapy in B-cell Non-Hodgkin Lymphomas.
Radiation and Chimeric Antigen Receptor T-cell Therapy in B-cell Non-Hodgkin Lymphomas.
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CAR-T 细胞疗法(CAR-T)是化疗难治性B细胞非霍奇金淋巴瘤治疗中的一项革命性进展,在既往仅能进行姑息治疗的情形下,代表了一种潜在可治愈的疗法。CAR-T 细胞疗法伴随独特的毒性以及实际挑战。其中一个挑战是如何在长达数周的CAR-T 制造过程中管理活动性淋巴瘤。放疗、类固醇和全身治疗均已被用于这一时间段内所谓的“桥接治疗”。放疗是一种特别有吸引力的策略,因为其在化疗难治性淋巴瘤中已证实有效;能够稳定患者病情、减瘤和缓解症状;以及其增强CAR-T 细胞扩增和活性的潜力。最佳剂量、时机和给药方法尚未确立,尽管共识认为如果用作治疗前桥接,应在白细胞分离术后进行。另一个实际挑战是CAR-T 细胞治疗失败患者的管理。在特定患者中,挽救性放疗可能具有新兴作用,可用于姑息治疗或作为使患者获得另一种潜在治愈性治疗的手段。需要协作良好的前瞻性临床试验来明确确立放疗(CAR-T 治疗前或治疗后)的作用,以及确定其对CAR-T 细胞活性/持久性和相关毒性的影响。
Chimeric antigen receptor T-cell therapy (CAR-T) is a revolutionary advancement in the management of chemotherapy refractory B-cell non-Hodgkin lymphomas representing a potentially curative therapy in scenarios that were previously only palliative. CAR-T cell therapy is associated with unique toxicities as well as practical challenges. One of those challenges is how to manage active lymphoma during the weeks-long CAR-T manufacturing process. Radiation therapy, steroids, and systemic therapy have all been used for what would be considered "bridging therapy" during this time frame. Radiation therapy is a particularly attractive strategy given its proven efficacy in chemotherapy refractory lymphomas; ability to stabilize patients, debulk disease, and palliate symptoms; as well as its potential to enhance the expansion and activity of CAR-T cells.
Optimal dose, timing, and method of delivery are yet to be established though there is consensus that it should occur after apheresis if being used as a pre-treatment bridge. Another practical challenge is the management of patients in whom CAR-T cells fail.
There is a potential emerging role for salvage radiation therapy, in select patients, for either palliation or as a means to get patients another potentially curative therapy. Collaborative well-designed prospective clinical trials are needed to definitively establish the role for radiation therapy (before or after CAR-T therapy) as well as define the impact on CAR-T cell activity/persistence and associated toxicity.
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